PB1935: CARDIOTOXICITY AND SAFETY OF BRUTON’S TYROSINE KINASE INHIBITORS: A REVIEW OF REAL-WORLD OBSERVATIONAL EVIDENCE
Authors: Chakrapani Balijepalli, Gaye Siliman, Juhi Joshy, Lakshmi Gullapalli, Eric Druyts
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Bruton’s tyrosine kinase (BTK) inhibitors have been investigated as potential treatment options for B-cell malignancies. First generation BTK inhibitors exhibited significant efficacy and tolerability compared to standard chemoimmunotherapy in clinical trials, with long term follow-up incidence of cardiotoxicities being observed and leading to treatment discontinuation in some patients. Incidence of cardiotoxicities and subsequent treatment discontinuation was shown to be lower with second generation BTK inhibitors in clinical trials. Aims: We aimed to compare the cardiotoxicity and safety of first and second-generation BTK inhibitors in the treatment of B-cell malignancies in real-world observational studies. Methods: We performed a systematic literature review of real-world observational studies conducted in patients treated with BTK inhibitors. We collected data on incidence of atrial fibrillation, hypertension, treatment discontinuation due to progression, and treatment discontinuation due to adverse events. We conducted a random effects meta-analysis of pooled proportions. Results: This systematic literature review included 83 real-world observational studies, of which 77 studies had a first generation BTK inhibitor, and 6 studies included a second generation BTK inhibitor treatment. The median duration of follow-up in first generation BTK inhibitor studies ranged from 8.7 months to 42 months, while for second generation studies it ranged from 5 months to 42.3 months. Incidence of atrial fibrillation of any grade was 7.2% (95% CI 5.3-9.4) for first generation BTK inhibitors and 3.4% (95% CI 1.7-5.6) for the second generation BTK inhibitors. Hypertension incidence for any grade was 9% (95% CI 4.8-14.1) for the first generation BTK inhibitors; data on this outcome was not available for the second generation BTK inhibitors. Treatment discontinuation due to adverse events was 15.6% (95% CI 12-19.5) and 5% (95% CI 0.0-14) for the first and second generation BTK inhibitors respectively. Treatment discontinuation due to disease progression was 14.4% (95% CI 11-18.2) and 13% (95% CI 1.8-30.4) for the first and second generation BTK inhibitors respectively. Summary/Conclusion: This study demonstrated that the incidence of atrial fibrillation, treatment discontinuation due to adverse events and disease progression was slightly higher in the patients treated with first generation BTK inhibitors in real-world observational studies. However, it was not possible to directly compare first and second generation BTK inhibitors using real-world observational data. Real-world observational data for the second generation BTK inhibitors was very limited. Given the current state of evidence, a discussion of whether these results are clinically meaningful should continue until further evidence becomes available. Keywords: Bruton’s tyrosine kinase inhibitor (BTKi), Safety